The overall objective of the project is to relate the early events which cause loss of arterial intimal integrity to the final intimal thickening which leads to the late consequences of atherosclerosis. The work is divided into four major areas. The first consists of in vivo rabbit and rat studies in which the response to single and multiple arterial ballon catheter injury is being investigated. Specifically, the studies will try to elucidate the mechanism by which de-endothelialized vessels limit their response to injury. Studies utilizing the hypophysectomized rat are designed to explore the role of platelet derived smooth muscle cell mitogen in the proliferative response. In the second area the role of fibronectin and other membrane glycoprotein in the attachment and detachment of endothelial cells will be studied in a tissue culture system. In the third major area, the role of certain other intracellular and transmembrane proteins in endothelial cell attachment will be investigated by immunologic and chemical means. Finally, studies will be undertaken to characterize and localize the membrane-associated and extracellular proteoglycans and to determine if these macromolecular proteins modulate platelet vessel wall interaction. Thus, the biochemical studies will attempt to understand the molecular events governing limited proliferative response defined in the animal studies of the first project.